Our general research objectives are to continue our studies on the biochemical and structural mechanisms of the pathologic effects produced by ethanol with an interdisciplinary team especially interested in hepatology, gastroenterology, pathology, biochemistry, nutrition, metabolism and hematology. Our ultimate goal is the application of this information to the prevention and treatment of diseases associated with alcoholism. We plan to determine whether cirrhosis can be produced in the absence of dietary deficiencies, or, if potentiation of the alcohol effect by dietary abnormalities is found to be necessary, to define the respective roles of various dietary components. If cirrhosis is successfully produced, transition from fatty liver to cirrhosis will be assessed by chemical and ultrastructural analysis of serial liver biopsies in rats and primates, including the studies of kinetics of cell proliferation. Alterations of the structure and functions of the endoplasmic reticulum of hepatocytes will be studied after acute and chronic ethanol induced injury. The sequence of the ultrastructural organelle changes produced by ethanol will be determined and assessment will be made of the amount of ethanol required to produce hepatic injury. Special attention will be given to possible effects of alterations of endoplasmic reticulum on the metabolism of psychotropic drugs through changes in drug detoxifying enzymes. We shall continue our search for potential protective agents against alcohol induced hepatic injury; optimal drug and dietary treatment of patients with alcoholic fatty liver will be defined.